Influence of different asparaginase formulations in the prognosis of children with acute lymphocytic leukaemia in Brazil: a multicentre, retrospective controlled study
Mariana Bohns Michalowski
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorCorresponding Author
Daiane Keller Cecconello
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Correspondence: Dr. Mariana Bohns Michalowski, Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
E-mail: [email protected]
Search for more papers by this authorMecneide Mendes Lins
Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE, Brazil
Search for more papers by this authorMaria do Perpétuo Socorro Sampaio Carvalho
Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas, Manaus, AM, Brazil
Search for more papers by this authorKlerize Anecely de Souza Silva
Hospital da Criança Conceição, Porto Alegre, RS, Brazil
Search for more papers by this authorLilian Cristofani
Instituto de Tratamento do Câncer Infantil, São Paulo, SP, Brazil
Search for more papers by this authorThais Alcantra Bonilha
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, RJ, Brazil
Search for more papers by this authorBianca Faustini Baglioli
Hospital de Câncer de Barretos, Barretos, SP, Brazil
Search for more papers by this authorMara Albonei Dudeque Pianovski
Hospital Erasto Gaertner, Curitiba, PR, Brazil
Search for more papers by this authorAna Paula Kuczynski
Hospital Pequeno Príncipe, Curitiba, PR, Brazil
Search for more papers by this authorPablo Santiago
Universidade de Passo Fundo, Passo Fundo, RS, Brazil
Search for more papers by this authorCiliana Rechenmacher
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAna Paula Alegretti
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorKarla Rodrigues
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorMariana Rodrigues de Magalhães
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorLiane Esteves Daudt
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorMariana Bohns Michalowski
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorCorresponding Author
Daiane Keller Cecconello
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Correspondence: Dr. Mariana Bohns Michalowski, Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
E-mail: [email protected]
Search for more papers by this authorMecneide Mendes Lins
Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE, Brazil
Search for more papers by this authorMaria do Perpétuo Socorro Sampaio Carvalho
Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas, Manaus, AM, Brazil
Search for more papers by this authorKlerize Anecely de Souza Silva
Hospital da Criança Conceição, Porto Alegre, RS, Brazil
Search for more papers by this authorLilian Cristofani
Instituto de Tratamento do Câncer Infantil, São Paulo, SP, Brazil
Search for more papers by this authorThais Alcantra Bonilha
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, RJ, Brazil
Search for more papers by this authorBianca Faustini Baglioli
Hospital de Câncer de Barretos, Barretos, SP, Brazil
Search for more papers by this authorMara Albonei Dudeque Pianovski
Hospital Erasto Gaertner, Curitiba, PR, Brazil
Search for more papers by this authorAna Paula Kuczynski
Hospital Pequeno Príncipe, Curitiba, PR, Brazil
Search for more papers by this authorPablo Santiago
Universidade de Passo Fundo, Passo Fundo, RS, Brazil
Search for more papers by this authorCiliana Rechenmacher
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Search for more papers by this authorAna Paula Alegretti
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorKarla Rodrigues
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorMariana Rodrigues de Magalhães
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorLiane Esteves Daudt
Translational Pediatrics Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
Search for more papers by this authorSummary
Our group recently showed that the (ASNase) formulation available in Brazil from 2017 to 2018 when used at the same dose and frequency as the formulation provided previously did not reach the activity considered therapeutic. Based on these, our goal was to assess the impact of these facts on the prognosis of children with ALL at different oncology centers. A multicentre retrospective observational study followed by a prospective follow-up. Patients aged >1 and <18 years in first-line treatment followed up at 10 referral centres, between 2014 and 2018 who received the formulation Leuginase® were identified (Group B). For each patient, the centre registered 2 patients who received ASNase in the presentation of Aginasa® exclusively (Group A). Data collection was registered using (Redcap®). A total of 419 patients were included; 282 in Group A and 137 in B. Group A had a 3-year OS and EFS of 91·8% and 84·8% respectively, while Group B had a 3-year OS of 83·8% (P = 0·003) and EFS of 76·1% (P = 0·008). There was an impact on 3-year OS and EFS of children who received a formulation. This result highlights the importance of evaluating ASNase and monitoring its activity.
Conflict of interest
The authors declare declare to have no potential conflicts of interest regarding the present work.
References
- 1Howlader N, Noone AM, Krapcho M. SEER Cancer Statistics Review (CSR) 1975-2013. Bethesda, MD: National Cancer Institute, 2015. Available online. Last accessed February 13, 2020.
- 2De Camargo B, de Oliveira SM, Rebelo MS, Reis JS, Ferman S, Noronha CP, et al. Cancer incidence among children and adolescent in Brazil: first report of 14 population-based cancer registries. Int J Cancer. 2010; 126: 715–20.
- 3Pieters R, Hunger SP, Boos J, Rizzari C, Silverman L, Baruchel A, et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer. 2011; 117: 238–49.
- 4de Sousa DWL, Ferreira FVA, Félix FHC, Lopes MVO. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival. Rev Bras Hematol Hemoter. 2015; 7: 223–9.
10.1016/j.bjhh.2015.03.009 Google Scholar
- 5Schrey D, Borghorst S, Lanvers-Kaminsky C, Hempel G, Gerß J, Möricke A, et al. Therapeutic drug monitoring of asparaginase in the ALL-BFM 2000 Protocol Between 2000 and 2007. Pediatr Blood Cancer. 2010; 54: 952–8.
- 6Cecconello DK, Magalhaes MR, Werlang ICR, Lee MLM, Daudt LE, Michalowski MB. Asparaginase: an old drug with new questions. Hematol Transf Cell Therap. 2019; 1379: 30142–7.
- 7Barbaa P, Dapena JL, Montesinos P, Rives S. Asparaginase use for the treatment of acute lymphoblastic leukemia. Med Clin (Barc). 2017; 148: 225–31.
- 8van der Sluis IM, Vrooman LM, Pieters R, Baruchel A, Escherich G, Goulden N, et al. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica. 2016; 101: 279–85.
- 9Avramis VI, Tiwari PN. Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. Int J Nanomedicine. 2006; 1: 241–54.
- 10Salzer W, Bostrom B, Messinger Y, Perissinotti AJ, Marini B. Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia. J Leuk Lymphoma. 2018; 59(8): 1797–806.
- 11Nadeem K, Colantonio D, Kircanski I, Naqvi A, Hitzler J, Whitlock JA, et al. Clinical decisions following implementation of asparaginase activity monitoring in pediatric patients with acute lymphoblastic leukemia: Experience from a single-center study. Pediatr Blood Cancer. 2020; 67(2):e28044.
- 12Boos J, Werber G, Ahlke E, Schulze-Westhoff P, Nowak-Göttl U, Würthwein G, et al. Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparations. Eur J Cancer. 1996; 32: 1544–50.
- 13Cecconello DK, Werlang ICR, Alegretti AP, Hahn MC, de Magalhães MR, Battistel AP, et al. Monitoring asparaginase activity in middle-income countries. Lancet Oncol. 2018; 19: 1149–50.
- 14Zenatti PP, Migita NA, Cury NM, Mendes-Silva RA, Gozzo FC, de Campos-Lima PO, et al. Low bioavailability and high immunogenicity of a new brand of E. coli l-asparaginase with active host contaminating proteins. EBioMedicine. 2018; 30: 158–66.
- 15Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009; 42: 377–81.
- 16Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L,, et al.; REDCap Consortium. The REDCap consortium: building an international community of software partners. J Biomed Inform. 2019. https://doi.org/10.1016/j.jbi.2019.103208.
- 17Brandalise SR, Pinheiro VR, Lee MLM. Protocolo de Tratamento da Leucemia Linfoblástica Aguda da Criança e do Adolescente - GBTLI LLA - 2009. Unpublished [protocol]; Brazil, 2009.
- 18Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91–01. Blood. 2001; 97: 1211–8.
- 19Ogawa C, Ohara A, Manabe A, Hanada R, Takahashi H, Koh K, et al. Treatment outcome of discontinued L-asparaginase in children with standard-risk acute lymphoblastic leukemia: Tokyo Children’s Cancer Study Group (TCCSG) Study L99–15 [abstract]. Blood. 2005; 106: 878.
- 20Ertel IJ, Nesbit ME, Hammond D, Sather H. Effective dose of L-asparaginase for induction of remission in previously treated children with acute lymphocytic leukemia: a report from Childrens Cancer Study Group. Cancer Res. 1979; 39: 3893–6.
- 21Amylon MD, Shuster J, Pullen J, Berard C, Link MP, Wharam M, et al. Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study. Leukemia. 1999; 13: 335–42.
- 22Sallan SE, Gelber RD, Kimball V, Donelly M, Cohen HJ. More is better! Update of Dana-Farber Cancer Institute/Children’s Hospital Childhood acute lymphoblastic leukemia trials. Haematol Blood Transfus. 1990; 33: 459–66.
- 23Duval M, Suciu S, Ferster A, Rialland X, Nelken B, Lutz P, et al. Comparison of Escherichia coli–asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: Results of a randomized European Organisation for Research and Treatment of Cancer—Children's Leukemia Group phase 3 trial. Blood. 2002; 99: 2734–9.
- 24Wetzler M, Sanford BL, Kurtzberg J, DeOliveira D, Frankel SR, Powell BL, et al. Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: cancer and leukemia group B study 9511. Blood. 2007; 109: 4164–7.
- 25Gupta S, Wang C, Raetz EA, Schore R, Salzer WL, Larsen EC, et al. Impact of asparaginase discontinuation on outcome in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group. J Clin Oncol. 2020; 38: 1897–905.
- 26van der Sluis IM, Groot-Kruseman H, te Loo M, Tissing WJE, den Boss CV, Kaspers GJL, et al. Efficacy and safety of recombinant E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: a randomized multicenter study of the Dutch Childhood Oncology Group. Pediatr Blood Cancer. 2018; 65(8):e27083.
- 27Vyasa C, Jaina S, Kapoor G, Mehta A, Chugh PT. Experience with generic pegylated L-asparaginase in children with acute lymphoblastic leukemia and monitoring of serum asparaginase activity. Pediatr Hematol Oncol. 2018; 35: 331–40.
- 28Sankaran H, Sengupta S, Purohit V, Kotagere A, Moulik NR, Prasad M, et al. A comparison of asparaginase activity in generic formulations of E.coli derived L- asparaginase: in-vitro study and retrospective analysis of asparaginase monitoring in pediatric patients with leukemia. Br J Clin Pharmacol. 2020; 86: 1081–8.
- 29Cecconello DK, Rechenmacher C, Werlang I, Zenatti PP, Yunes JA, Alegretti AP, et al. Implementation of the asparaginase activity assessment technique for clinical use: experience of a Brazilian Center. Sci Rep. 2020; 10: 21481.
Citing Literature
